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  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 4 ( 2020-02-20), p. 1426-
    Abstract: Variably reduced expression of the basement membrane component laminin-332 (α3aβ3γ2) causes junctional epidermolysis bullosa generalized intermediate (JEB-GI), a skin fragility disorder with an increased susceptibility to squamous cell carcinoma (SCC) development in adulthood. Laminin-332 is highly expressed in several types of epithelial tumors and is central to signaling pathways that promote SCC tumorigenesis. However, laminin-332 mutations and expression in individuals affected by JEB-GI and suffering from recurrent SCCs have been poorly characterized. We studied a JEB-GI patient who developed over a hundred primary cutaneous SCCs. Molecular analysis combined with gene expression studies in patient skin and primary keratinocytes revealed that the patient is a functional hemizygous for the p.Cys1171* mutant allele which is transcribed in a stable mRNA encoding for a β3 chain shortened of the last two C-terminal amino acids (Cys1171-Lys1172). The lack of the Cys1171 residue involved in the C-terminal disulphide bond to γ2 chain did not prevent assembly, secretion, and proteolytic processing of the heterotrimeric molecule. Immunohistochemistry of SCC specimens revealed accumulation of mutant laminin-332 at the epithelial-stromal interface of invasive front. We conclude that the C-terminal disulphide bond is a structural element crucial for laminin-332 adhesion function in-vivo. By saving laminin-332 amount, processing, and signaling role the p.Cys1171* mutation may allow intrinsic pro-tumorigenic properties of the protein to be conveyed, thus contributing to invasiveness and recurrence of SCCs in this patient.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: Antibiotics, MDPI AG, Vol. 10, No. 5 ( 2021-04-30), p. 512-
    Abstract: Background: Peri-implantitis is a pathological condition characterized by an inflammatory process involving soft and hard tissues surrounding dental implants. The management of peri-implant disease has several protocols, among which is the chemical method HYBENX®. The aim of this study is to demonstrate the efficacy of HYBENX® in the treatment of peri-implantitis and to compare HYBENX® with other chemical agents used in the surgical treatment of peri-implantitis. Methods: The present study included a population of ten subjects with severe peri-implantitis. The procedure used in the study involves the application of HYBENX® after open-flap debridement. Each patient has been followed for 12 months after a single application of the decontaminant agent. Clinical and radiographical parameters were recorded at baseline, 3 months, and 12 months after treatment completion. Results: At baseline, a mean pocket probing depth (PPD) of 7.3 ± 0.5 mm and a mean clinical attachment level (CAL) of 8.8 ± 0.8 mm was recorded. An average residual PPD of 4.2 ± 0.5 mm and a mean CAL of 5.2 ± 0.8 mm were observed after 1 year. Additionally, the average of bone gain was about 3.4 mm, with a mean marginal bone level (MBL) change from 5.8 mm (baseline) to 2.4 mm (12 months). In total, 90% of the treated implants reached the success rate after the 1-year follow-up. Only in one case out of ten treated implants was resolution of the disease not achieved. Conclusion: Clinical improvements highlight that the procedure of open-flap debridement (OFD) + HYBENX® may be considered an effective technique in the treatment of peri-implantitis. From the results obtained, it can be concluded that the use of HYBENX® in the surgical treatment of peri-implantitis is promising. Overall, this protocol demands further studies to better understand the role and potential benefits of HYBENX® in the treatment of peri-implantitis.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 3
    In: Biomedicines, MDPI AG, Vol. 9, No. 12 ( 2021-12-16), p. 1930-
    Abstract: Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected. Thereafter, we isolated TILs from seven freshly surgically removed melanomas and from three basal cell carcinomas (BCC), as a comparison with a non-melanoma skin cancer known to retain a high amount of Th17 cells. In both studies, we found that, differently from BCC, melanoma samples showed a lower percentage of Th17 lymphocytes. Additionally, TIL clones could not be induced to differentiate towards the Th17 phenotype in vitro. The presence or absence of Th17 cells did not correlate with any patient characteristics. We only observed a lower amount of Th17 cells in samples from woman donors. We found a tendency towards an association between expression by melanoma cells of placenta growth factor, angiogenic factors able to induce Th17 differentiation, and presence of Th17 lymphocytes. Taken together, our data indicate the necessity of a deeper analysis of Th17 lymphocytes in cutaneous melanoma before correlating them with prognosis or proposing Th17-cell based therapeutic approaches.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  International Journal of Environmental Research and Public Health Vol. 15, No. 3 ( 2018-03-03), p. 439-
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 15, No. 3 ( 2018-03-03), p. 439-
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2175195-X
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  • 5
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 9 ( 2018-09-06), p. 2652-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 9 ( 2018-09-06), p. 2652-
    Abstract: Human keratinocytes were recently shown to respond to anti-EGFR (epidermal growth factor receptor) drugs with activation of an interferon-κ-driven autocrine loop, leading to enhanced expression of innate antiviral effectors and of the pro-inflammatory chemokines CXCL10 (C-X-C motif chemokine 10) and CCL2 (C-C motif ligand 2). Here we showed active type I interferon signaling in the skin lesions of cancer patients undergoing treatment with the anti-EGFR drug cetuximab. Strong nuclear positivity for Interferon Regulatory Factor 1 and phosphorylated Signal Transducer and Activator of Transcription 1, enhanced interferon-κ expression and CXCL10 was associated to the epidermal compartment. Notably, 50 micromolar resveratrol and quercetin fully suppressed the low constitutive levels of type I interferon signaling and prevented its activation by the anti-EGFR cetuximab or gefitinib in cultured keratinocytes. In sensitized mice undergoing DNFB (2,4-dinitro-1-fluorobenzene)-induced contact hypersensitivity, local administration of gefitinib prior to elicitation further amplified hapten-induced type I interferon activation, tissue edema, and infiltration by T cells, whereas resveratrol or quercetin suppressed this inflammatory cascade. Overall, these data suggest that topical application of resveratrol or quercetin could be potentially effective in preventing pathological conditions due to overactivation of type I IFN (interferon)-driven circuits in the skin, including the inflammatory manifestations of anti-EGFR drug-induced skin-targeted toxicity.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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